title: Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery.
abstract: Bypass of the foregut following Roux-en-Y gastric bypass (RYGB) surgery results in altered nutrient absorption, which is proposed to underlie the improvement in glucose tolerance and insulin sensitivity. We conducted a prospective crossover study in which a mixed meal was delivered orally before RYGB (gastric) and both orally (jejunal) and by gastrostomy tube (gastric) postoperatively (1 and 6 wk) in nine subjects. Glucose, insulin, and incretin responses were measured, and whole-body insulin sensitivity was estimated with the insulin sensitivity index composite. RYGB resulted in an improved glucose, insulin, and glucagon-like peptide-1 (GLP-1) area under the curve (AUC) in the first 6 wk postoperatively (all P ≤ 0.018); there was no effect of delivery route (all P ≥ 0.632) or route × time interaction (all P ≥ 0.084). The glucose-dependent insulinotropic polypeptide (GIP) AUC was unchanged after RYGB (P = 0.819); however, GIP levels peaked earlier after RYGB with jejunal delivery. The ratio of insulin AUC to GLP-1 and GIP AUC decreased after surgery (P =.001 and 0.061, respectively) without an effect of delivery route over time (both P ≥ 0.646). Insulin sensitivity improved post-RYGB (P = 0.001) with no difference between the gastric and jejunal delivery of the mixed meal over time (P = 0.819). These data suggest that exclusion of nutrients from the foregut with RYGB does not improve glucose tolerance or insulin sensitivity. However, changes in the foregut response post-RYGB due to lack of nutrient exposure cannot be excluded. Our findings suggest that foregut bypass may alter the incretin response by enhanced nutrient delivery to the hindgut.
authors.affiliation: Departments of Surgery, Vanderbilt Univ. School of Medicine, Nashville, TN 37232-2730, USA.
authors.forename: Erik N
authors.initials: EN
authors.lastname: Hansen
authors.forename: Robyn A
authors.initials: RA
authors.lastname: Tamboli
authors.forename: James M
authors.initials: JM
authors.lastname: Isbell
authors.forename: Jabbar
authors.initials: J
authors.lastname: Saliba
authors.forename: Julia P
authors.initials: JP
authors.lastname: Dunn
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Marks-Shulman
authors.forename: Naji N
authors.initials: NN
authors.lastname: Abumrad
mesh_terms: D000328:Adult; D000713:Anastomosis, Roux-en-Y; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004386:Duodenum / Q000502:physiology*; D005260:Female; D005502:Food; D015390:Gastric Bypass; D054439:Ghrelin / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007583:Jejunum / Q000502:physiology*; D010535:Laparoscopy; D008297:Male; D008660:Metabolism / Q000502:physiology; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D054795:Incretins; D007328:Insulin; D052216:Glucagon-Like Peptide 1